ABSTRACT Atrial fibrillation (AF) is the most common rhythm disturbance in the US and other developed countries. AF significantly affects the lives of the afflicted, causing symptoms that range from palpitations to fatigue, weakness and activity intolerance, and substantially increasing the risks of stroke, congestive heart failure and death. The impact on public health is substantial, with more than 450,000 hospital admissions per year and $26 billion in healthcare costs. Adding to the problems caused by AF is the lack of safe and effective therapies for this rhythm disorder. Pharmacotherapy for AF has a long history of poor efficacy and potentially lethal side effects. Ablation strategies are making inroads in paroxysmal AF, but they are long, difficult procedures with less than optimal success rates and too frequent adverse events. We propose gene therapy as a new strategy to treat AF. We have published efficacy and safety data in a pig model of AF showing that interventions to prevent or reverse electrical and structural remodeling can eliminate the ability of the atria to fibrillate. To date, our atrial gene painting delivery method has required chest-opening surgery which will ultimately limit clinical utility. Here, we propose development of a delivery catheter that will allow atrial gene painting from a percutaneous approach to the pericardial space. To develop this catheter, we propose the following specific aims: (1) to verify performance of the gene painting catheter in bench top testing, (2) to confirm complete and specific atrial painting with the percutaneous catheter in acute animal studies. Successful completion of these aims will provide critical design and feasibility data that will move us toward our ultimate goal of curing AF with gene therapy.